Interleukin-1 ("IL-1") is a cytokine which is known to be a key mediator of immunological and pathological responses to stress, infection and antigenic challenge (Oppenheim et al., Immunol. Today 7:45-46, 1986; Dinarello, FASEB J. 2:108-115, 1988; and Mizel, FASEB J. 3:2379-2388, 1989). In addition, IL-1 is known to have a variety of effects on the brain and central nervous system. For example, IL-1 has been postulated to be involved in the induction of fever (Kluger, Physiol. Rev. 71:93-127, 1991), increased duration of slow wave sleep (Opp et al., Am. J. Physiol. 260:R52-R58, 1991), decreased appetite (McCarthy et al., Am. J. Clin. Nutr. 42:1179-1182, 1985), activation of the hypothalamic-pituitary-adrenal ("HPA") axis (Woloski et al., Science 230:1035-1037, 1985), and inhibition of the hypothalamic-pituitary-gonadal axis (River and Vale, Endocrinology 124:2105-2109, 1989).
In light of the above-noted effects of IL-1 (as well as many others), substantial effort has been undertaken in order to identify receptors for IL-1. Briefly, at least two types of receptors are known to be expressed on the surface of certain immune cells in both human and murine derived lines. Type I receptors bind both IL-1.alpha. and IL-1.beta., and can be found on T cells, fibroblasts, keratinocytes, endothelial cells, synovial lining cells, chondrocytes and hepatocytes (U.S. Pat. Nos. 4,968,607, 5,081,228, and 5,180,812; Chizzonite et al., PNAS 86:8029-8033, 1989; Dinarello et al., Blood 77:1627-1652, 1991). Type II receptors can be found on various B cell lines, including the Raji human B-cell lymphoma line (Bomsztyk et al., PNAS 86:8034-8038, 1989; Horuk et al., J. Biol. Chem. 262:16275-16278, 1987; Horuk and McCubrey, Biochem. J. 260:657-663, 1989).
The present invention provides new, previously unidentified Interleukin receptors, designated Interleukin-1 Type 3 receptors ("IL-1-3R"). In addition, the present invention provides compositions and methods which utilize such receptors, as well as other, related advantages.